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Michael House receives four-year NIH research grant

05/06/2017

Michael House, MD is a maternal-fetal medicine physician at Tufts Medical Center.Michael House, MD, a MIRI Principal Investigator and Maternal Fetal Medicine Physician at Tufts Medical Center, has received a four-year R01 from the National Institutes of Health (NIH) for the development of a silk-based injectable gel to prevent preterm birth.  The gel will be used for women with preterm cervical shortening, which is a well-known risk factor associated with preterm birth.  The idea of the gel is to augment cervical tissue to prevent preterm cervical shortening and dilation, which is a novel treatment strategy compared with existing treatments.

Preterm birth itself affects more than 500,000 births a year in the US, or approximately 12.3% of all pregnancies. 

Dr. House will collaborate with Dr. David Kaplan, the Professor & Chair of Biomedical Engineering at Tufts University and the Director of the NIH Tissue Engineering Resource Center.  Dr. Kaplan’s research focus is biopolymer engineering, and his laboratory’s study of silk-based biomaterials in regenerative medicine is its specific expertise.  Both laboratories will work closely together on the development and assessment of the silk-protein based gel and its experimental use in pregnant animals.

The gel is primarily composed of purified silk protein.  “The silk protein starts off as a liquid and then we use a chemical reaction to create cross links – chemical bonds between the different silk polymers that make the fluid silk solidify into a gel,” Dr. House explained.

The first objective of the study is to develop the gel to meet tissue augmentation design goals, such as mechanical properties (softness, stiffness, elasticity), gelation time, and functionalization to promote properties that are desirable for interaction with the cellular environment.

The gel will then be assessed for functional performance.  One of these assessments is degradation time, since the gel will act as a temporary bulking agent.  “We don’t want to put a permanent gel in the body, so biodegradability is both essential and a design challenge,” Dr. House noted.  Another functional test is cell binding, which is “tricking” the cell into thinking it is supported by the extracellular matrix, when it is actually supported by the gel. Assessments will also be performed by adding proteins to the gel to influence the cell’s immune response.

After mechanical and functional assessments are done, the cervical tissue augmentation properties of the gel will be tested in an animal model of pregnancy, to evaluate what happens in cervical tissue during pregnancy.  Experiments will evaluate the mechanical properties, degradation times, and biocompatibility of the gel. 

Dr. House’s experience as an ob/gyn doctor and a biomechanical engineer contribute to his particular perspective in developing the silk-based gel.  Preterm birth is a complicated problem with multiple causes, not all of them related to cervical dysfunction.  However, an effective, injectable gel to prevent premature cervical shortening and dilation will have a highly significant impact on the treatment of preterm birth related to cervical dysfunction.